Histology of Lymphomas with t(3;14)(q27;q32) Correlates with the Molecular Anatomy of the Translocation.

The t(3;14)(q27;q32) is the most common translocation involving BCL6 in non Hodgkin B-cell lymphoma. Although this translocation has been predominantly associated with diffuse large B-cell lymphoma (DLBCL), recent studies have shown that it can also be found in follicular lymphomas (FL), where it is often associated with a large cell component. To further investigate the relationship that might exist between this translocation and the phenotype of the tumor, we studied 34 B-cell lymphomas with t(3;14)(q27;q32) and diffuse or follicular growth patterns. As the t(3;14)(q27;q32), involving telomeric ends of both chromosomes 3 and 14, is often difficult to detect by conventional cytogenetic, it should be emphasised that only t(3;14) positive FL or DLBCL where the translocation could be validated either by molecular technics (cloning of the breakpoint, amplification of specific IGH-BCL6 fusion transcripts or fluorescence in situ hybridization) were retained in this study. Noteworthy, none of the samples were found to have a t(14;18), indicating that the two most frequent translocations in B-cell NHL, both seen as early transforming events, are usually exclusive. This observation is in agreement with the hypothesis that BCL2 and BCL6 deregulations probably constitute two different lymphomagenesis pathways. Our data also indicate that most t(3;14) positive DLBCL share a CD10⁻/BCL6⁺/MUM1⁺ phenotype (10/16, 62%) and can be classified in the non-germinal centre subgroup (12/16, 75%)%), while a majority of t(3;14) positive FL are CD10⁻ and BCL6⁺ (10/12, 83%). Moreover, we identified the IGH switch region (S) involved in the translocation for 32 cases, either by cloning the genomic breakpoint (27 cases), and/or by amplifying the IGH-BCL6 fusion transcripts expressed by the tumors (26 cases). For 17/19 (89%) DLBCL or FL with DLBCL, the translocation involved the Sμ, while for 9/13 (70%) FL with no diffuse areas of proliferation the t(3;14) involved a Sγ. These results indicate that the histology of the tumor and the structure of the translocated allele are correlated (p=0.0016), suggesting that the substituted regulatory regions that comes to deregulate BCL6 after a t(3;14) may affect the presentation of the disease.